The foundation for the proposed hypothesis of this application assumes three critical steps to carcinogenesis as studied in the Syrian hamster kidney tumor model: 1) hormonal stimulation, 2) metabolic activation, 3) free radical generation. The specific aims are to: 1) clone and characterize Syrian hamster ER cDNA; 2) study the effect of metabolic activation/free radical generation of ER gene expression; 3) characterize the role of metabolic/estrogenic potential on cell specific expression of ER proteins on tumorigenesis in hamster kidneys; and 4) investigate the role of metabolic activation of estrogens and the interdependency of, if any, between overexpression and neu suppression.